Cytokinetics Incorporated : 2025 Annual Report of 2025
CYTK
Published on 04/17/2026 at 07:24 pm EDT
DEAR SHAREHOLDER,
Muscles empower our everyday lives. They enable movement, sustain function and enable possibilities. For more than two decades, Cytokinetics' steady and disciplined research in muscle biology focused on understanding the mechanics of muscle at its most fundamental level with the unwavering goal of translating that pioneering
science into medicines for patients. 2025 defined a major milestone for our company and culmination of that aspiration, meeting the moment with the approval of our first medicine.
In December 2025, the FDA approved MYQORZO® (aficamten) for adults with obstructive hypertrophic cardiomyopathy (oHCM). MYQORZO was also approved in China in 2025, and in the European Union in early 2026, positioning us for commercial launches in key global geographies. These corporate achievements defined a turning of the page onto a new chapter in our company's history as Cytokinetics has now become a global commercial biotechnology company.
Like a finely tuned orchestra, we met the moment together with crescendo. Years of R&D rigor, operational planning and readiness, and thoughtful fiscal management aligned at the right time to enable fulfillment of our longstanding mission. All in, making this happen called upon our collective convictions, purpose-driven execution, and persistent resilience in the face of complexity and uncertainties. Throughout last year, we scaled up in numbers and geographies, expanded teams and strengthened capabilities, enabling us to launch MYQORZO in the United States promptly following receipt of FDA approval.
While 2025 will be remembered as the year of our first regulatory approvals, it was also a year of continued pipeline advancement.
We presented results from MAPLE-HCM, the Phase 3 clinical trial evaluating aficamten as monotherapy compared to metoprolol in patients with oHCM, with simultaneous publication in the New England Journal of Medicine. This landmark trial demonstrated that aficamten improved exercise capacity, while metoprolol showed a detrimental effect, challenging a long-standing treatment paradigm in HCM and marking an important inflection point in how this disease may ultimately be treated in the future.
We also completed enrollment in ACACIA-HCM, the pivotal Phase 3 clinical trial of aficamten in non-obstructive HCM (nHCM), a population representing roughly half of all HCM patients. We expect to report top-line results from this trial in Q2 2026. Together, MAPLE-HCM and ACACIA-HCM, if positive, may provide evidence to potentially inform changes to treatment guidelines.
While HCM remains the anchor of our emerging specialty cardiology franchise, we also continued our later-stage development programs in 2025 focused on two different forms of heart failure. We continued enrolling patients in COMET-HF, the Phase 3 clinical trial of omecamtiv mecarbil in patients with heart failure with severely reduced ejection fraction (HFrEF), and AMBER-HFpEF, the Phase 2 clinical trial of ulacamten in patients with heart failure with preserved ejection fraction (HFpEF). Each of these two clinical-stage programs reflects our commitment to applying our expertise in muscle biology to diseases of impaired contractility and building a robust pipeline designed to ensure sustainable growth as well as longer-term value for our emerging specialty cardiology franchise.
As we have entered our first year as a commercial-stage company, we do so with a stronger financial foundation and flexibility in accessing additional capital. Our disciplined capital management provided the cash runway necessary to successfully execute our launch strategies, invest in pipeline advancement and to support our global expansion planning.
We look to the future for Cytokinetics with humility and determination. The approval of MYQORZO is not the end of a journey, but a new beginning with opportunities and responsibilities.
We are now even more determined to build on the momentum of 2025, guided by our Vision 2030, and focused on delivering meaningful value to shareholders. Successes in 2026 and beyond will demand continued focus, innovation and disciplined excellence. With our signature grit, resilience and pride in purpose, we are not standing still but instead are accelerating. We are Flexing our Muscles. We are immensely grateful to scientists who pursued discovery with integrity, employees who steadfastly delivered, partners who stood beside us, and patients who have entrusted us with their hope.
Robert I. Blum
President and Chief Executive Officer
Drug Candidate
Therapeutic Area
Research
Pre-Clinical Phase 1 Phase 2 Phase 3
Approved and Commercialized
MYQORZO®* oHCM
Aficamten
oHCM
(vs. metoprolol)
Approved in U.S., China & EU
Aficamten Pediatric oHCM
Aficamten
nHCM**
Ulacamten
Omecamtiv Mecarbil
HFpEF
HFrEF
CK-089
Muscular Dystrophy, other
Research
Muscle Biology Directed
* Please see full Prescribing Information, including Boxed WARNING at https://cytokinetics.com/pi_myqorzo. ** Phase 3 topline results expected in Q2 2026
MYQORZO is only approved in the U.S., China and EU for the treatment of adults with symptomatic oHCM.
Ulacamten, omecamtiv mecarbil and CK-089 are investigational drug candidates and are not approved as safe or effective for any indication.
(Mark One)
Washington, D.C. 20549
☑ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended December 31, 2025 or
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
From the transition period from to Commission file number: 000-50633
(Exact name of registrant as specified in its charter)
Delaware 94-3291317
(State or other jurisdiction of incorporation or organization)
350 Oyster Point Boulevard
(I.R.S. Employer Identification No.)
South San Francisco, CA 94080
(Address of principal executive offices) (Zip Code)
(650) 624-3000
(Registrant's telephone number, including area code)
Securities registered pursuant to Section 12(b) of the Act:
Title of each class Common Stock, $0.001 par value
Trading symbol CYTK
Name of each exchange on which registered The Nasdaq Global Select Market
Securities registered pursuant to Section 12(g) of the Act: None
Indicate by check mark if the Registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☑ No ☐
Indicate by check mark if the Registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No ☑
Indicate by check mark whether the Registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes
☑ No ☐
Indicate by check mark whether the Registrant has submitted electronically Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes ☑ No ☐
Indicate by check mark whether the Registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of "large accelerated filer," "accelerated filer," "smaller reporting company," and "emerging growth company" in Rule 12b-2 of the Exchange Act.
Large accelerated filer ☑ Accelerated filer ☐ Non-accelerated filer ☐ Smaller reporting company ☐ Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
Indicate by check mark whether the registrant has filed a report on and attestation to its management's assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C.7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☑
If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the Registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐
Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the Registrant's executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐
Indicate by check mark whether the Registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☑
The approximate aggregate market value of voting and non-voting common stock held by non-affiliates of the Registrant was $2.5 billion as of June 30, 2025.(A)
(A) Excludes 43.8 million shares of common stock held by directors and executive officers, and any stockholders known to us whose ownership exceeded ten percent of our common stock outstanding as of June 30, 2025. Exclusion of shares held by any person should not be construed to indicate that such person possesses the power, directly or indirectly, to direct or cause the direction of the management or policies of the registrant, or that such person is controlled by or under common control with the registrant.
As of February 23, 2026, the number of shares outstanding of the Registrant's common stock, par value $0.001 per share, was 123,162,807 shares.
DOCUMENTS INCORPORATED BY REFERENCE
Portions of the Registrant's Proxy Statement for its 2026 Annual Meeting of Stockholders to be filed with the Securities and Exchange Commission, no later than 120 days after the end of the fiscal year, are incorporated by reference into Part III of this Annual Report on Form 10-K.
CYTOKINETICS, INCORPORATED FORM 10-K
YEAR ENDED DECEMBER 31, 2025 INDEX
Item 1. Item 1A. Item 1B. Item 1C. Item 2.
Item 3.
Item 4.
Item 5.
Item 6.
Item 7. Item 7A. Item 8.
Item 9. Item 9A. Item 9B. Item 9C.
Item 10.
Item 11.
Item 12.
Item 13.
Item 14.
Item 15.
Glossary of Terms..............................................................................................................................................
Forward Looking Statements Private Securities Litigation Reform Act of 1995 .............................................
PART I
Business .............................................................................................................................................................
Risk Factors .......................................................................................................................................................
Unresolved Staff Comments..............................................................................................................................
Cybersecurity.....................................................................................................................................................
Properties ...........................................................................................................................................................
Legal Proceedings..............................................................................................................................................
Mine Safety Disclosures....................................................................................................................................
PART II
Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities............................................................................................................................................................
[Reserved]..........................................................................................................................................................
Management's Discussion and Analysis of Financial Condition and Results of Operations............................ Quantitative and Qualitative Disclosures About Market Risk ..........................................................................
Financial Statements and Supplementary Data .................................................................................................
Changes in and Disagreements with Accountants on Accounting and Financial Disclosure ........................... Controls and Procedures....................................................................................................................................
Other Information ..............................................................................................................................................
Disclosure Regarding Foreign Jurisdictions that Prevent Inspections ..............................................................
PART III
Directors, Executive Officers and Corporate Governance ................................................................................ Executive Compensation ...................................................................................................................................
Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters ......... Certain Relationships and Related Transactions, and Director Independence .................................................. Principal Accountant Fees and Services............................................................................................................
PART IV
Exhibits and Financial Statement Schedules .....................................................................................................
Page
3
6
7
25
40
40
42
42
43
44
45
46
59
60
95
95
97
97
98
98
98
98
98
99
Exhibits.......................................................................................................................................................................................... 99
Item 16.
Form 10-K Summary.........................................................................................................................................
103
Signatures ...................................................................................................................................................................................... 104
GLOSSARY OF TERMS
Unless the context requires otherwise, references to "Cytokinetics," "the Company," "we," "us" or "our" in this Form 10-K refer to Cytokinetics, Incorporated and its subsidiaries. References to "Notes" in this Form 10-K are to the Notes to the Consolidated Financial Statements in this Form 10-K. We also have used other specific terms in this Form 10-K, most of which are explained or defined below:
Term/Abbreviation Definition
2004 Plan Cytokinetics' Amended and Restated 2004 Equity Incentive Plan
2022 RPI Transactions The transactions contemplated by the RP Multi Tranche Loan Agreement and the RP
Aficamten RPA
2024 RPI Transactions
The transactions contemplated by the 2024 RP OM Loan Agreement, the RP
Ulacamten RPA, the RP Stock Purchase Agreement, the 2022 RP Multi Tranche Loan Agreement Amendment and the RP Aficamten RPA Amendment
2026 Indenture Indenture, dated November 13, 2019, between Cytokinetics and U.S. Bank Trust Company (successor in interest to U.S. Bank National Association), as trustee, as supplemented by the First Supplemental Indenture, dated November 13, 2019, between Cytokinetics and U.S. Bank Trust Company (successor in interest to U.S. Bank National Association)
2026 Notes Cytokinetics' 4% convertible senior notes due 2026
2027 Indenture Indenture, dated July 6, 2022, between Cytokinetics and U.S. Bank Trust Company, as trustee
2027 Notes Cytokinetics' 3.50% convertible senior notes due 2027
2031 Indenture Indenture, dated September 19, 2025, between Cytokinetics and U.S. Bank Trust Company, as trustee
2031 Notes Cytokinetics' 1.75% convertible senior notes due 2031
ACACIA-HCM Assessment Comparing Aficamten to Placebo on Cardiac Endpoints In Adults with Non-Obstructive HCM
AMBER-HFpEF
Our Phase 2 randomized, placebo-controlled, double-blind, multi-center, dose-finding
clinical trial in patients with symptomatic HFpEF with left ventricular ejection fraction ≥ 60%
Astellas FSRA Agreement
Fast Skeletal Regulatory Activator Agreement, dated April 23, 2020 between
Cytokinetics and Astellas
Amended ATM Facility Our amended and restated Controlled Equity Offering Sales Agreement
Bayer Means Bayer AG and/or any affiliate thereof, including Bayer Consumer Care AG
Bayer License Agreement
Means that certain License and Collaboration Agreement, dated November 18, 2024
by and between the Company and Bayer Consumer Care AG, pursuant to which Bayer acquired an exclusive license to develop and commercialize aficamten in Japan, subject to certain reserved development rights.
CEDAR-HCM Our clinical trial of aficamten in a pediatric population with oHCM
Cantor Cantor Fitzgerald & Co.
cGCP Current Good Clinical Practice
cGLP Current Good Laboratory Practice
cGMP Current Good Manufacturing Practice
China People's Republic of China (including the Hong Kong and Macau SARs)
CMC Chemistry, Manufacturing and Controls
CMO Contract Manufacturing Organizations
COMET-HF Our Phase 3 multi-center, double-blind, randomized, placebo-controlled trial to assess the efficacy and safety of omecamtiv mecarbil in patients with symptomatic HFrEF with severely reduced ejection fraction
Common Stock Our common stock, par value $0.001 per share
Compensation Committee Compensation and Talent Committee of Cytokinetics' Board of Directors
Convertible Notes 2026 Notes, 2027 Notes, and 2031 Notes
Corxel Corxel Pharmaceuticals Limited (formerly known as Ji Xing Pharmaceuticals Limited) and/or its affiliates, including Corxel Pharmaceuticals Hong Kong Limited
Corxel OM License Agreement
Means that certain Collaboration and License Agreement, dated December 20, 2021,
by and between the Company and Corxel, pursuant to which we granted Corxel an exclusive license to develop and commercialize omecamtiv mecarbil in China and Taiwan
COURAGE-ALS Clinical Outcomes Using Reldesemtiv on ALSFRS-R in a Global Evaluation in ALS
CRO Contract Research Organization
CV Cardiovascular
E.U. or EU European Union
EMA European Medicines Agency
ESPP Employee Stock Purchase Plan
ETASU Elements to assure safe use
Exchange Act Securities Exchange Act of 1934, as amended
FDA U.S. Food and Drug Administration
Final Payment Amount
As defined in Part II, Item 7 (Management's Discussion and Analysis of Financial
Conditions and Results of Operations) of this Annual Report on Form 10-K - Sources and Uses of Cash, Royalty Pharma Transactions
FOREST-HCM Five-Year, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in HCM
Fundamental Change As defined in the 2026 Indenture, 2027 Indenture, or 2031 Indenture, as applicable
GAAP Generally Accepted Accounting Principles in the U.S.
GALACTIC-HF
Global Approach to Lowering Adverse Cardiac Outcomes Through Improving
Contractility in Heart Failure
GDPR General Data Protection Regulation ((EU) 2016/679)
HCM Hypertrophic cardiomyopathy
HFpEF Heart failure with preserved ejection fraction
HFrEF Heart failure with reduced ejection fraction
HHS U.S. Department of Health and Human Services
HIPAA
The federal Health Insurance Portability and Accountability Act of 1996, as amended
by the Health Information Technology for Economic and Clinical Health Act
IND Investigational New Drug
IRA Inflation Reduction Act of 2022
KCCQ Kansas City Cardiomyopathy Questionnaire
KCCQ-OSS KCCQ Overall Summary Score
LVEF Left ventricular ejection fraction
LVOT Left ventricular outflow tract
LVOT-G Left ventricular outflow tract gradient
MAA Marketing Authorization Application
MAPLE-HCM Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Endpoints Capacity in HCM
NDA New Drug Application
nHCM Non-obstructive HCM
NOLs Net operating loss carryforward
NYHA New York Heart Association
oHCM Obstructive HCM
Oyster Point Lease Lease, dated July 24, 2019, by and between Cytokinetics and KR Oyster Point 1, LLC, as amended
Partial Redemption Limitation As defined in the 2027 Indenture and 2031 Indenture, as applicable
PSU Performance Stock Unit
Radnor Lease
As defined in Part II, Item 8 (Financial Statements and Supplementary Data), Notes to
Consolidated Financial Statements of this Annual Report on Form 10-K - Note 9 (Commitments and Contingencies) - Operating Leases
REMS Risk Evaluation and Mitigation Strategy
RP Aficamten RPA
Revenue Participation Right Purchase Agreement, dated January 7, 2022, by and
between Cytokinetics and Royalty Pharma Investments 2019 ICAV
RP Aficamten RPA Amendment Amendment No. 1, dated May 22, 2024, to Revenue Participation Right Purchase
Agreement, dated January 7, 2022, by and between Cytokinetics and Royalty Pharma Investments 2019 ICAV
RP Ulacamten RPA
Ulacamten Revenue Participation Right Purchase Agreement, dated May 22, 2024, by
and between Cytokinetics and Royalty Pharma Investments 2019 ICAV
RP Multi Tranche Loan Agreement Development Funding Loan Agreement, dated January 7, 2022, by and among
Royalty Pharma Development Funding, LLC and Cytokinetics
RP Multi Tranche Loan Agreement Amendment
Third Amendment, dated May 22, 2024, to Development Funding Loan Agreement, dated January 7, 2022, by and among Royalty Pharma Development Funding, LLC and Cytokinetics
RP OM Liability As defined in Part II, Item 8 (Financial Statements and supplementary Data), Notes to Consolidated Financial Statements of this Annual Report on Form 10-K - Note 3 (Agreements with Royalty Pharma) - 2017 RP Omecamtiv Mecarbil Royalty Purchase Agreement
RP OM Loan Agreement
2024 Development Funding Loan Agreement, dated May 22, 2024, by and among
Royalty Pharma Development Funding, LLC and Cytokinetics
RP OM RPA Royalty Purchase Agreement, dated February 1, 2017, by and between Cytokinetics and RPI Finance Trust, as amended by Amendment No. 1, dated January 7, 2022
RP Stock Purchase Agreement
Common Stock Option and Purchase Agreement, dated May 22, 2024, by and
between Cytokinetics and Royalty Pharma Investments 2019 ICAV
RPDF Royalty Pharma Development Funding, LLC
RPFT RPI Finance Trust
RPI ICAV Royalty Pharma Investments 2019 ICAV
RSU Restricted Stock Unit
Sanofi Means Sanofi S.A. and/or any affiliates thereof, including Genzyme Corporation
Sanofi License Agreement
Means that certain License and Collaboration Agreement, dated July 14, 2020 by and
between the Company and Sanofi (as assignee of Corxel), pursuant to which Sanofi has an exclusive license to develop and commercialize aficamten in China and Taiwan
Section 382 Section 382 of the Internal Revenue Code
Securities Act Securities Act of 1933, as amended
SEQUOIA-HCM Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM
SGLT2 Sodium-glucose cotransporter-2
U.S. or US United States of America
This Form 10-K includes discussion of certain clinical studies relating to various in-line products and/or product candidates. These studies typically are part of a larger body of clinical data relating to such products or product candidates, and the discussion herein should be considered in the context of the larger body of data. In addition, clinical trial data are subject to differing interpretations, and, even when we view data as sufficient to support the safety and/or effectiveness of a product candidate or a new indication for an in-line product, regulatory authorities may not share our views and may require additional data or may deny approval altogether.
CYTOKINETICS and our C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries.
Other service marks, trademarks and trade names referred to in this report are the property of their respective owners.
The information contained on our website, our Facebook, Instagram, YouTube and LinkedIn pages or our X (formerly Twitter) accounts, or any third-party website, is not incorporated by reference into this Form 10-K.
FORWARD LOOKING STATEMENTS
PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995
This Annual Report on Form 10-K contains forward-looking statements within the meaning of Section 27A of the Securities Act and Section 21E of the Exchange Act. All statements other than statements of historical fact, including statements concerning our plans, objectives, goals, strategies, future events, future revenues or performance, financing needs, expectations, plans or intentions relating to clinical development, product candidates, the regulatory approval process, our commercialization efforts for MYQORZO, products and markets, and business trends and other information referred to under the "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations," are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as "anticipate," "assume," "believe," "commitment," "could," "estimate," "expect," "forecast," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would," "seek" and similar expressions intended to identify forward-looking statements. We have made these statements in reliance on the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are subject to certain risks and uncertainties, which could cause actual results, outcomes, and the timing of events to differ materially from the results discussed in the forward-looking statements.
In addition, these forward-looking statements are subject to the risks and uncertainties discussed in the "Risk Factors" section and elsewhere in this document. Such statements speak only as of the date on which they are made, and, except as required by law, we undertake no obligation to update any forward-looking statement to reflect events or circumstances after the date on which the statement is made or to reflect the occurrence of unanticipated events. New factors emerge from time to time, and it is not possible for us to predict which factors will arise. In addition, we cannot assess the impact of each factor on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements.
In addition, statements that "we believe" and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this Annual Report on Form 10-K, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements.
PART I
ITEM 1. BUSINESS
Overview
We are a biopharmaceutical company focused on discovering, developing and commercializing novel muscle activators and muscle inhibitors as potential treatments for debilitating diseases in which muscle performance is compromised and/or declining. We have discovered and are developing muscle-directed investigational medicines that may potentially improve the healthspan of people with devastating cardiovascular and neuromuscular diseases of impaired muscle function. Our first commercial product is MYQORZO™ (aficamten), 5 mg, 10 mg, 15 mg, and 20 mg tablets, which the FDA approved in December 2025. MYQORZO is an allosteric and reversible inhibitor of cardiac myosin motor activity. The approval of MYQORZO included a risk evaluation and mitigation strategy (REMS) program to ensure the benefits of the drug outweigh the risk of heart failure due to systolic dysfunction. In patients with oHCM, myosin inhibition with MYQORZO reduces cardiac contractility and left ventricular outflow tract obstruction. MYQORZO became available for prescription to patients on or around January 27, 2026. In addition, in February 2026, the European Commission approved MYQORZO® (aficamten), 5 mg, 10 mg, 15 mg and 20 mg tablets for the treatment of symptomatic (New York Heart Association, NYHA, class II-III) oHCM in adult patients. Moreover, in December 2025, the China National Medical Products Administration approved MYQORZO for the treatment of adults with (New York Heart Association class II-III) oHCM, to improve exercise capacity and symptoms.
Behind MYQORZO, we are making disciplined pipeline investments in investigational products that are at discovery, preclinical and clinical stages of research and development. All our research and development activities relate to the biology of muscle function and have evolved from our knowledge and expertise regarding the cytoskeleton, a complex biological infrastructure that plays a fundamental role within every human cell. As a leader in muscle biology and the mechanics of muscle performance, we are discovering and developing small molecule drug candidates specifically engineered to impact muscle function and contractility with the objective of building a sustainable specialty biopharmaceutical business.
Our specific focus on the biology of the cytoskeleton distinguishes us from other biopharmaceutical companies and potentially positions us to identify or discover and develop and commercialize novel therapeutics that may be useful for the treatment of severe diseases and medical conditions. We intend to leverage our experience in muscle contractility to expand our current pipeline and expect to identify additional potential drug candidates that may be suitable for clinical development and commercialization.
Corporate Strategy
We are discovering, developing and commercializing small molecule drugs and drug candidates specifically engineered to modulate muscle function to improve patient healthspan. With the approval of our first medicine, MYQORZO, we have transitioned into a fully-integrated specialty biopharmaceutical company.
In 2025, we articulated our five-year strategic plan, Vision 2030: "Empowering Muscle, Empowering Lives," designed to enable Cytokinetics to become a leading muscle biology specialty biopharmaceutical company intent on meaningfully improving the lives of patients through global access to our innovative medicines.
The key components of our five-year corporate strategy are:
INNOVATION: Advance 2 product approvals across 3 indications and 10 novel molecular entities into our pipeline
Our myosin platform is the cornerstone of our innovation and the anchor of our portfolio of medicines and potential medicines is MYQORZO. MYQORZO was approved in December 2025 by the FDA for treatment of adults with symptomatic oHCM to improve functional capacity and symptoms and the China National Medical Products Administration for the treatment of adults with (New York Heart Association class II-III) oHCM to improve exercise capacity and symptoms. In February 2026, the European Commission approved MYQORZO® (aficamten), 5 mg, 10 mg, 15 mg and 20 mg tablets for the treatment of symptomatic (New York Heart Association, NYHA, class II-III) obstructive hypertrophic cardiomyopathy in adult patients. Over the next five years, based on our comprehensive clinical development program, we believe we may achieve regulatory approvals in other geographies for aficamten in oHCM, as well as regulatory approvals in multiple geographies for nHCM, subject to the results of ACACIA-HCM, our Phase 3 clinical trial evaluating the use of aficamten in patients with nHCM. Subject to the results of COMET-HF, we may also potentially achieve regulatory approvals for omecamtiv mecarbil for the treatment of symptomatic heart failure with severely reduced ejection fraction. We also intend to advance two earlier stage new chemical entities in clinical development programs: (i) ulacamten for the potential treatment of a subgroup of patients with symptomatic HFpEF with hypercontractility and ventricular hypertrophy and
(ii) CK-089, which has potential therapeutic application to a specific type of muscular dystrophy and other conditions of impaired muscle function. Furthermore, we have the objective to bring additional new product candidates into clinical development through both internal research activities and by leveraging external collaborators, seeking complementary potential therapies to support our late-stage cardiovascular franchise and emerging neuromuscular pipeline.
IGNITION: Achieve broad access and rapid use of our medicines in 15 countries throughout North America and Europe
Given our focus on disease areas for which there are serious unmet medical needs, we direct our activities to potential commercial opportunities in concentrated and tractable customer segments, such as to disease-specific centers of excellence and cohorts of focused healthcare professionals, that may be addressed by targeted sales forces. In preparing for the commercialization of MYQORZO, we built a marketing, sales and sales distribution infrastructure in the U.S., and in light of the European Commission approving MYQORZO® (aficamten), 5 mg, 10 mg, 15 mg and 20 mg tablets for the treatment of symptomatic (New York Heart Association, NYHA, class II-III) obstructive hypertrophic cardiomyopathy in adult patients, we are also preparing for a commercial launch in Europe in 2026, initially in Germany, to be followed by other major European countries. In addition, we have entered into licensing agreements with Sanofi in China and Bayer in Japan and expect to establish additional licensing or distribution arrangements in other areas of the world to drive accessibility of our medicines to patients worldwide. Central to our commercialization strategy is having a clear understanding and expertise in navigating the regulatory and payer landscape in each geography along with market research and advanced analytics to inform positioning, messaging and value proposition development
IMPACT: Reach 100,000 patients globally with our medicines.
As we build our specialty cardiology franchise, beginning with the commercialization of MYQORZO, we are committed to targeting disease areas of high unmet need in which there are either limited treatment options or in which the available treatments do not address the underlying disease. We believe there are hundreds of thousands of patients who may benefit from clinically meaningful outcomes delivered by our science focused on the biology of muscle function, as measured by improvements in clinical, social and psychological aspects, including patients' overall quality of life.
INSPIRATION: Foster a patient-centric culture with an emphasis on equitable access
We consider patients as we advance research, clinical development and commercialization. By prioritizing systematic patient engagement, we foster a culture of empathy and collaboration, ensuring that the voice of the patient remains central to our decision-making process. In line with our patient-centric approach, we proactively seek to include patients from diverse populations in our clinical trials, representative of real-world experience, including a range of genders, ethnicities, socioeconomic status and backgrounds. In commercializing our first medicine, we aspire to provide equitable access for all patients regardless of gender, ethnicity or location and we are developing programs for patients and healthcare providers to facilitate access accordingly. These programs may include support to help understand and navigate insurance coverage and obtain financial assistance for eligible patients; comprehensive patient and office education and resources to help navigate the patient's treatment journey, support to manage logistical challenges that prevent patients from starting and staying on therapy and behavioral and wellness tools and resources to support patient engagement and help manage adherence to treatment.
INGENUITY: Extend leadership in muscle deploying multiple therapeutic modalities
After expanding our discovery platform to include muscle mechanics, muscle metabolism, and muscle health and regeneration, we are seeking to expand our research modalities to better enable our programs to address more difficult-to-drug molecular targets. This diversification in modalities will allow us to interrogate areas adjacent to our expertise in small molecules, such as targeted protein degraders, oligonucleotides and tissue targeting. With these additional modalities in our R&D armamentarium, we expect to have the opportunity to investigate disease causing targets that lack enzymatic activities, require near complete inhibition for clinical efficacy or have adverse effects in non-target tissues. We believe we can expand into new modalities through a combination of building internal expertise and capabilities and through external collaborations with industry partners and academic institutions.
Building a Specialty Cardiology Franchise
We believe we are well positioned to build a specialty cardiology franchise anchored by MYQORZO and, later complemented by earlier stage drug candidates that have arisen from our research and leadership in muscle biology and the mechanics of contractility. We anticipate that MYQORZO, the first approved product in our business franchise, will help serve unmet needs in the growing oHCM market. In addition to the oHCM market, if results from ACACIA-HCM are positive and support filing for registration, aficamten may receive regulatory approval for the treatment of adult patients with symptomatic nHCM. We further believe that our pioneering research directed to the same biology and emerging pharmacology could result in an expansion of our business franchise with the development and potential approval of ulacamten for the treatment of a subset of patients with HFpEF whose hypercontractility resembles that of patients with nHCM, as well as the development and potential approval of omecamtiv mecarbil, a cardiac myosin activator, for the treatment of patients with symptomatic heart failure with severely reduced ejection fraction.
Our specialty cardiology franchise is focused on advancing MYQORZO and other potential medicines that can address the high unmet needs of patients primarily treated by a concentrated segment of cardiologists. Specifically, HCM is primarily diagnosed and treatment initiated by approximately 10,000 cardiologists in the U.S., including in both academic centers of excellence and targeted community settings. We aim to achieve commercial returns from our targeted specialty franchise business by deploying experienced sales representatives with established rapport with their potential customers and by coupling their selling activities with high-touch customer support services designed to support prescribers and patients alike.
Cytokinetics' Marketed Product: MYQORZO™
MYQORZO™ (aficamten), is a novel, oral, small molecule cardiac myosin inhibitor that our scientists discovered for the treatment of symptomatic oHCM. MYQORZO was designed to reduce the hypercontractility associated with HCM. In preclinical models, MYQORZO reduces myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering a force producing state. MYQORZO reduces the number of active actin-myosin cross bridges during each cardiac cycle and consequently reduces myocardial contractility.
HCM is the most common monogenic inherited cardiovascular disorder, with well over 300,000 patients diagnosed in the U.S. However, there are an estimated 400,000-800,000 additional patients who remain undiagnosed. The diagnosis rate for oHCM is growing at approximately the same rate as the population, while the diagnosis rate for nHCM has been increasing with recent year-over-year growth estimated to be in the low double digits. Estimates vary but we believe approximately half of patients with HCM have oHCM, in which the thickening of the cardiac muscle leads to LVOT obstruction, while the remaining HCM patients have nHCM, in which blood flow is not impacted, but the heart muscle is still thickened. HCM is fairly evenly split across gender and while patients are typically diagnosed in their early 40s, the average age of an oHCM patient is in the early 60s. People with HCM are at high risk of also developing cardiovascular complications, including atrial fibrillation, stroke and mitral valve disease. People with HCM are at risk for potentially fatal ventricular arrhythmias, and HCM is one of the leading causes of sudden cardiac death in younger people or athletes. A subset of patients with HCM are at high risk of progressive disease leading to dilated cardiomyopathy and heart failure necessitating cardiac transplantation.
In December 2025, the FDA approved MYQORZO, 5 mg, 10 mg, 15 mg, and 20 mg tablets for the treatment of adults with symptomatic oHCM to improve functional capacity and symptoms. MYQORZO is an allosteric and reversible inhibitor of cardiac myosin motor activity. The approval of MYQORZO included a risk evaluation and mitigation strategy (REMS) program to ensure the benefits of the drug outweigh the risk of heart failure due to systolic dysfunction. In addition, in February 2026, the European Commission approved MYQORZO® (aficamten), 5 mg, 10 mg, 15 mg and 20 mg tablets for the treatment of symptomatic (New York Heart Association, NYHA, class II-III) obstructive hypertrophic cardiomyopathy (oHCM) in adult patients. Moreover, in December 2025, the China National Medical Products Administration approved MYQORZO for the treatment of adults with (New York Heart Association class II-III) oHCM, to improve exercise capacity and symptoms.
We commenced commercial sales of MYQORZO in the United States in the first quarter of 2026 and expect to report our first commercial revenues in May 2026 in our Quarterly Report on Form 10-Q for the fiscal quarter ending March 31, 2026. Our market research supports our belief that MYQORZO will be highly competitive amongst cardiac myosin inhibitors, potentially eventually achieving a greater than 50% market share in the United States but also growing the cardiac myosin inhibitor category overall. We expect Sanofi to commence commercializing activities in China in 2026.
The commercial prospects for MYQORZO are based on three launch drivers: clinical evidence, our experience with HCPs and patients, and the approved label. Clinical evidence shows that treatment with MYQORZO in adult patients with symptomatic oHCM led to rapid and sustained reduction in obstruction and improvement in symptoms. Our experience with HCPs and patients informed our Cardiac Account Specialist (CAS) design, including its single point of contact and accountability for HCP's with our field sales organization and our bespoke patient support program, MYQORZO and You™..
We believe the MYQORZO prescribing information allows for flexibility to titrate as early as two weeks, with echo assessment within 2 to 8 weeks following dose initiation and any subsequent dose changes, and importantly, a patient's dose may be titrated as needed after each echo with no delay.
In the European Union, MYQORZO is approved for the treatment of symptomatic (New York Heart Association, NYHA, class II-III) oHCM in adult patients and anticipate commencing commercialization activities in Germany in the second quarter of 2026 to be followed by other major European countries. MYQORZO is approved in China for the treatment of adults with (New York Heart Association class II-III) oHCM, to improve exercise capacity and symptoms. We depend on Sanofi for commercialization of MYQORZO in China.
Finally, in January 2026 we submitted a supplemental NDA for MYQORZO to the FDA requesting to include the results of MAPLE-HCM, a Phase 3 randomized, double blind, active-comparator clinical trial of aficamten as monotherapy compared to metoprolol as a monotherapy in patients with obstructive HCM, in the label. Assuming a standard review period, we expect a potential approval of the supplemental NDA by the FDA in the fourth quarter of 2026.
Research and Development Programs
Our research and development activities related to muscle contractility include our cardiac muscle contractility programs and our skeletal muscle contractility programs. We also conduct research and development on novel treatments for disorders involving muscle function beyond muscle contractility.
Specialty Cardiology Programs
Our specialty cardiology program is focused on the cardiac sarcomere, the basic unit of muscle contraction in the heart. The cardiac sarcomere is a highly ordered cytoskeletal structure composed of cardiac myosin, actin and a set of regulatory proteins. Cardiac myosin is the cytoskeletal motor protein in the cardiac muscle cell. It is directly responsible for converting chemical energy into the mechanical force, resulting in cardiac muscle contraction. Our most advanced cardiac program, MYQORZO (aficamten), is based on the hypothesis that inhibitors of cardiac myosin may attenuate the hyperdynamic contraction resulting from pathologic mutations in the sarcomere that lead to hypertrophic cardiomyopathies. MYQORZO was approved in the U.S., Europe and China for the treatment of adults with symptomatic oHCM. We submitted a supplemental NDA to the FDA in January 2026 with the intent to include the results of MAPLE-HCM (a Phase 3 randomized, double blind, active-comparator clinical trial of aficamten as monotherapy compared to metoprolol as a monotherapy in patients with obstructive HCM) in the label. Finally, as described below, we are evaluating aficamten for the potential treatment of adults with symptomatic nHCM in ACACIA-HCM.
In addition, omecamtiv mecarbil is our late-stage clinical program directed to the hypothesis that activators of cardiac myosin may target the underlying deficit of cardiac contractility in heart failure with severely reduced ejection fraction and address certain adverse properties of existing positive inotropic agents. Omecamtiv mecarbil is a novel cardiac myosin activator that works by directly stimulating the activity of the cardiac myosin motor protein, without increasing the intracellular calcium concentration. This drug candidate accelerates the rate-limiting step of the myosin enzymatic cycle and shifts it in favor of the force-producing state. Rather than increasing the velocity of cardiac contraction, this mechanism lengthens the systolic ejection time, which results in increased cardiac function in a potentially more oxygen-efficient manner.
Aficamten
Aficamten is a novel, oral, small molecule cardiac myosin inhibitor that our scientists discovered for the treatment of HCM. Aficamten arose from an extensive chemical optimization program conducted with attention to therapeutic index and pharmacokinetic properties. Aficamten was designed to reduce the hypercontractility associated with HCM. In preclinical models, aficamten reduces myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering a force producing state. Aficamten reduces the number of active actin-myosin cross bridges during each cardiac cycle and consequently reduces myocardial contractility. This mechanism of action may be therapeutically effective in conditions characterized by excessive hypercontractility, such as HCM. The preclinical pharmacokinetics of aficamten were characterized, evaluated and optimized for potential rapid onset, ease of titration and rapid symptom relief.
The FDA granted aficamten orphan drug designation for the treatment of symptomatic HCM in 2021.
The development program for aficamten has assessed its potential as a treatment to improve exercise capacity and relieve symptoms in patients with oHCM. In addition, development work is ongoing to assess aficamten for its potential long-term effects on cardiac structure and function.
Aficamten was evaluated in SEQUOIA-HCM, a positive pivotal Phase 3 clinical trial in patients with symptomatic oHCM. The results from SEQUOIA-HCM showed that treatment with aficamten for 24 weeks significantly improved exercise capacity compared to placebo, increasing peak oxygen uptake (pVO2) by 1.8 ml/kg/min compared to baseline in patients treated with aficamten versus
0.0 ml/kg/min in patients treated with placebo (p=0.000002). This treatment effect was consistent across all pre-specified subgroups, including patients receiving beta blockers. Statistically significant and clinically meaningful improvements were also observed in all 10 prespecified secondary endpoints, with functional and symptomatic improvements occurring within two weeks of initiating treatment with aficamten and sustained throughout the treatment period. There were no instances of worsening heart failure and no treatment interruptions due to low LVEF. Treatment emergent serious adverse events occurred in 5.6% of patients on MYQORZO (aficamten) and 9.3% of patients on placebo. Core laboratory echocardiographic LVEF was observed to be <50% in 5 patients (3.5%) on MYQORZO compared to 1 patient (0.7%) on placebo. Hypertension (8% vs 2%) was the only adverse reaction occurring in >5% of patients and more commonly on MYQORZO than on placebo. MYQORZO-associated increases in blood pressure are consistent with relief of LVOT obstruction and improved cardiac output. MYQORZO has been approved in the United States, the European Union, and China and, in each case as a treatment for adults with symptomatic oHCM.
Aficamten was also evaluated in MAPLE-HCM, a Phase 3 randomized, double blind, active-comparator clinical trial of aficamten as monotherapy compared to metoprolol as a monotherapy in patients with obstructive HCM. In May 2025, the company announced positive topline results from MAPLE-HCM and in August 2025 the company presented the primary results of MAPLE-HCM at the European Society of Cardiology Congress 2025. The primary endpoint in MAPLE-HCM was the mean change from baseline in pVO2 for aficamten compared to metoprolol after 24 weeks of treatment. MAPLE-HCM met its primary endpoint, demonstrating a statistically significant improvement in peak oxygen uptake (pVO2) from baseline to Week 24 for aficamten compared to metoprolol. For aficamten, the mean change in pVO2 from baseline to Week 24 was +1.1 mL/kg/min (95% CI 0.5 to 1.7) and for metoprolol was - 1.2 mL/kg/min (95% CI -1.7 to -0.8). The primary endpoint was statistically significant with a least-squares mean (LSM) difference between groups of 2.3 mL/kg/min (95% CI 1.5 to 3.1; p<0.0001). Overall, the rate of adverse events was similar between groups. At least one treatment-emergent adverse event was reported by 65 (73.9%) and 66 (75.9%) patients treated with aficamten and metoprolol, respectively. One patient receiving aficamten, a 69-year-old woman with multiple co-morbidities, developed a viral illness and subsequently died. Three patients receiving metoprolol terminated treatment due to adverse events. At least one treatment-emergent adverse event was reported by 65 (73.9%) and 66 (75.9%) patients treated with aficamten and metoprolol, respectively. The most common AE reported in excess (>5%) of the comparator was hypertension for aficamten (9 [10.2%] patients compared to 2 [2.3%] patients on metoprolol).
Aficamten continues to be evaluated in ACACIA-HCM, a Phase 3 clinical trial of aficamten in patients with nHCM; CEDAR-HCM, a clinical trial of aficamten in a pediatric population with oHCM; and FOREST-HCM, an open-label extension clinical study of aficamten in patients with HCM. We expect to report additional clinical data supporting a potential label expansion for aficamten in nHCM in the second quarter of 2026. We also expect to report complete enrollment in the adolescent cohort of CEDAR-HCM in the fourth quarter of 2026.
Collaboration for Commercialization of Aficamten in Greater China
We are party to a license and collaboration agreement, pursuant to which we granted to Corxel an exclusive license to develop and commercialize drug products containing aficamten in China and Taiwan. In the fourth quarter of 2024, Genzyme Corporation, an affiliate of Sanofi, acquired Corxel's rights to develop and commercialize drug products containing aficamten in China and Taiwan.
The China National Medical Products Administration approved MYQORZO (aficamten) for the treatment of adults with (New York Heart Association class II-III) oHCM, to improve exercise capacity and symptoms.
Collaboration for Commercialization of Aficamten in Japan
We are party to a collaboration and license agreement with Bayer Consumer Care AG, an affiliate of Bayer AG, for the exclusive development and commercialization of drug products containing aficamten in Japan, subject to certain reserved development rights of Cytokinetics to conduct ACACIA-HCM and CEDAR-HCM in Japan.
The first patient in Japan was dosed in ACACIA-HCM in the second quarter of 2025. The first patient was dosed in Bayer's Phase 3 clinical trial in oHCM, CAMELLIA-HCM, in Japan in the third quarter of 2025.
Royalty Pharma Revenue Interest
We are party to a revenue interest agreement with RPI ICAV, the RP Aficamten RPA, pursuant to which RPI ICAV purchased rights to certain revenue streams from net sales of MYQORZO and any other future potential pharmaceutical products containing aficamten by us, our affiliates and our licensees. Pursuant to the terms of the RP Aficamten RPA, as amended, RPI ICAV is entitled to receive 4.5% of our worldwide annual net sales of MYQORZO and any other future potential products containing aficamten up to
$5.0 billion and 1% of our annual net sales above $5.0 billion.
Omecamtiv mecarbil
We are developing omecamtiv mecarbil as a potential treatment across the continuum of care in heart failure with severely reduced ejection fraction both for use in the hospital setting and for use in the outpatient setting.
Omecamtiv mecarbil is a selective, small molecule cardiac myosin activator, the first of a novel class of myotropes designed to directly target the contractile mechanisms of the heart, binding to and recruiting more cardiac myosin heads to interact with actin during systole. Omecamtiv mecarbil is designed to increase the number of active actin-myosin cross bridges during each cardiac cycle and consequently augment the impaired contractility that is associated with heart failure with reduced ejection fraction, or HFrEF.
GALACTIC-HF
GALACTIC-HF is a Phase 3 cardiovascular outcomes clinical trial of omecamtiv mecarbil that was conducted by Amgen in collaboration with Cytokinetics. The primary objective of this double-blind, randomized, placebo-controlled multicenter clinical trial was to determine if treatment with omecamtiv mecarbil when added to standard of care is superior to standard of care plus placebo in reducing the risk of cardiovascular death or heart failure events in patients with high-risk chronic heart failure and reduced ejection fraction.
The results of GALACTIC-HF showed a statistically significant effect of treatment with omecamtiv mecarbil to reduce risk of the primary composite endpoint of CV death or heart failure events (heart failure hospitalization and other urgent treatment for heart failure) compared to placebo in patients treated with standard of care after a median duration of follow up of 21.8 months. A first primary endpoint event occurred in 1,523 of 4,120 patients (37.0%) in the omecamtiv mecarbil group and in 1,607 of 4,112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI] 0.86, 0.99; p=0.025). This effect was observed without evidence of an increase in the overall rates of myocardial ischemic events, ventricular arrhythmias or death from cardiovascular or all causes.
COMET-HF Informed by Results from Patient Subgroup in GALACTIC-HF
Since our release of the primary results of GALACTIC-HF, we have conducted and announced supplemental and subgroup analyses suggesting that certain biologically plausible subgroups of patients treated with omecamtiv mecarbil in GALACTIC-HF may have benefited more than the general patient population in the trial. Based on these and other promising subgroup analyses from GALACTIC-HF and the high unmet need in patients with heart failure with severely reduced ejection fraction, we are continuing the development program for omecamtiv mecarbil and conducting a confirmatory study in a patient population similar to the approximately 4,000 prespecified subgroup of patients with an LVEF <28% in GALACTIC-HF. Accordingly, in the fourth quarter of 2024, we commenced patient enrollment in COMET-HF (Confirmation of Omecamtiv Mecarbil Efficacy Trial in Heart Failure), a Phase 3 multi-center, double-blind, randomized, placebo-controlled trial to assess the efficacy and safety of omecamtiv mecarbil in patients with symptomatic HFrEF with severely reduced ejection fraction. The primary endpoint of COMET-HF is the time to first event in the primary composite endpoint of cardiovascular death, first heart failure event, LVAD implantation or cardiac transplantation, or stroke. COMET-HF is expected to enroll approximately 1,800 patients randomized on a 1:1 basis to receive omecamtiv mecarbil or placebo for up to 48 weeks.
Royalty Pharma Revenue Interest
In 2017, we entered into a Royalty Purchase Agreement, which we refer to as the RP OM RPA, with Royalty Pharma Development Funding, LLC, or RPFT, and amended the RP OM RPA on January 7, 2022. Pursuant to the RP OM RPA, as amended, RPFT has a revenue interest entitling it to up to 5.5% of our and our affiliates' and licensees' worldwide net sales of drug products containing omecamtiv mecarbil.
In the second quarter of 2024, we entered into the RP OM Loan Agreement with RPDF. Pursuant to the RP OM Loan Agreement, RDPF has a revenue interest entitling it to quarterly payments in an amount equal to 2.0% of the annual worldwide net sales of drug products containing omecamtiv mecarbil, subject to a minimum floor amount ranging from $5.0 million to $8.0 million during the first 18 calendar quarters commencing on the calendar quarter during which FDA approval for any drug product containing omecamtiv mecarbil is obtained, as further described in Note 3 to our consolidated financial statements included in this Annual Report on Form 10-K under the section "Agreements with Royalty Pharma," on the condition that a new Phase 3 clinical trial of omecamtiv mecarbil is successful by June 30, 2028 and we receive the marketing approval from the FDA for omecamtiv mecarbil on or prior to December 31, 2029.
Ulacamten (f/k/a CK-586)
Ulacamten is a novel, selective, oral, small molecule cardiac myosin inhibitor designed to reduce the hypercontractility associated with heart failure with preserved ejection fraction, or HFpEF. Approximately half of the estimated 6.7 million patients in the United States with heart failure have HFpEF, and the prevalence of HFpEF is increasing. A subset of HFpEF patients with hypercontractility, ventricular hypertrophy, elevated biomarkers and symptoms of heart failure may benefit from treatment with a cardiac sarcomere inhibitor. Approximately 75% of patients with HFpEF die within five years of initial hospitalization, and 84% are re-hospitalized. Despite broad use of standard treatments and advances in care, the prognosis for patients with heart failure is poor.
In preclinical models, ulacamten reduced cardiac hypercontractility by decreasing the number of active myosin cross-bridges during cardiac contraction thereby reducing the contractile force, without effect on calcium transients. Ulacamten selectively inhibits the ATPase of intact cardiac myosin but does not inhibit the ATPase of subfragment-1 of myosin (S1) as does aficamten, a cardiac myosin inhibitor we have also developed. Unlike aficamten, the inhibitory effect of ulacamten requires the presence of the regulatory light chain (RLC) of myosin in the context of the intact myosin dimer (heavy meromyosin or HMM). In engineered human HCM heart tissues, ulacamten demonstrated a shallow force-concentration response and improved lusitropy. Lending support for investigating this mechanism of action in HFpEF, a subset of patients with HFpEF resemble patients with non-obstructive hypertrophic cardiomyopathy (HCM) in that those patients have higher ejection fractions, thickened walls of their heart, elevated biomarkers, and symptoms of heart failure. Data from a Phase 2 clinical trial of aficamten in patients with nHCM show that aficamten was well tolerated, improved patient reported outcomes (Kansas City Cardiomyopathy Questionnaire (KCCQ) and New York Heart Association (NYHA) Functional Class) and biomarkers, measures that are also relevant to HFpEF.
Phase 1 Trial Results
We conducted a Phase 1 double-blind randomized, placebo-controlled, multi-part single and multiple ascending dose clinical study with the goal of evaluating the safety, tolerability and PK of ulacamten when administered orally as single or multiple doses to healthy participants. The primary objective of this clinical study was to evaluate the safety, tolerability and PK of ulacamten when administered orally to healthy participants. The study design included seven single ascending dose cohorts (10 mg to 600 mg) comprised of 10 participants each, and two multiple-dose cohorts (100 and 200 mg once daily) comprised of 10 participants each. This study data demonstrated that ulacamten was safe and well tolerated in healthy participants. No serious adverse events were observed and the stopping criteria for the study were not met. The half-life of ulacamten was observed to be in the range of 14 to 17 hours. Ulacamten demonstrated dose-linearity without a change in half-life over a wide range of exposures, with a steady-state appearing evident within seven days of dosing. Left ventricular ejection fraction and left ventricular fractional shortening decreased from baseline in an exposure-dependent manner, and the pharmacokinetic/pharmacodynamic relationship appeared shallow and predictable. At the highest single dose of 600 mg, the mean decrease in LVEF was <5%. These results demonstrate pharmacologic properties that may enable once-daily fixed-dose administration in the future.
AMBER-HFpEF
In the fourth quarter of 2024, we announced the design of AMBER-HFpEF (Assessment of Ulacamten in a Multi-Center, Blinded Evaluation of Safety and Tolerability Results in HFpEF), a Phase 2 randomized, placebo-controlled, double-blind, multicenter, dose-finding clinical trial in patients with symptomatic HFpEF with left ventricular ejection fraction ≥ 60%. The primary objective is to evaluate the safety and tolerability profile of ulacamten compared to placebo. The secondary objectives include assessing the effect of ulacamten on LVEF and NT-proBNP, its pharmacokinetics, and its pharmacokinetic/pharmacodynamic relationship. AMBER-HFpEF is currently enrolling patients, and we expect to complete enrollment in cohort 2 of the study by the end of 2026.
Royalty Pharma Revenue Interest
In the second quarter of 2024, we entered into a Revenue Participation Right Purchase agreement, which we refer to as the RP Ulacamten RPA, with RPI ICAV, pursuant to which RPI ICAV purchased rights to certain revenue streams from worldwide net sales of drug products containing ulacamten by us, our affiliates or licensees. Under the RP Ulacamten RPA, in consideration of an up-front
$50 million payment, RPI ICAV purchased a revenue interest entitling it to 1.0% of our annual worldwide net sales of drug products containing ulacamten. In addition, following the initiation of the first Phase 3 clinical trial (or the Phase 3 portion of the first Phase 2b/3 clinical trial) in heart failure with preserved ejection fraction in humans for ulacamten, RPI ICAV, at its sole discretion, has the right to purchase an additional revenue interest which if exercised would entitle it to an additional 3.5% of our annual worldwide net sales of drug products containing ulacamten in consideration of a payment equal to 50.0% of our future research and development costs of a Phase 3 trial of ulacamten up to a maximum of $150 million.
Neuromuscular Program
Our neuromuscular program is focused on the activation of the skeletal sarcomere, the basic unit of skeletal muscle contraction. The skeletal sarcomere is a highly ordered cytoskeletal structure composed of skeletal muscle myosin, actin, and a set of regulatory proteins, which include the troponins and tropomyosin. This program leverages our expertise developed in our ongoing discovery and development of cardiac sarcomere activator.
We believe that our skeletal sarcomere activators may lead to new therapeutic options for diseases and medical conditions associated with neuromuscular dysfunction and potentially also conditions associated with aging and muscle weakness and wasting. The clinical effects of muscle weakness and wasting, fatigue and loss of mobility can range from decreased quality of life to, in some instances, life-threatening complications. By directly improving skeletal muscle function, a small molecule activator of the skeletal sarcomere potentially could enhance functional performance and quality of life in patients suffering from diseases or medical conditions associated with skeletal muscle weakness or wasting.
In the fourth quarter of 2024, we announced that the first participants have been dosed in a Phase 1 randomized, double-blind, placebo-controlled, multi-part, single and multiple ascending dose clinical study of CK-089 in healthy human participants. CK-089 is a fast skeletal muscle troponin activator with potential therapeutic application to a specific type of muscular dystrophy and other conditions of impaired muscle function. The primary objective of this Phase 1 randomized, double-blind, placebo-controlled, multipart single and multiple ascending dose clinical study is to evaluate the safety, tolerability and pharmacokinetics of CK-089 when administered orally as single or multiple doses to healthy participants. The study design includes single ascending dose cohorts and multiple-dose ascending cohorts comprised of 10 participants each. Our clinical development program for CK-089 is subject to a partial clinical hold from FDA that limits our ability to dose patients at doses anticipated to result in plasma exposures higher than certain levels, which may limit the ability of our Phase 1 trial to identify a therapeutic dose for CK-089. We conducted a Phase 1 evaluation, and we are in ongoing discussions with regulatory authorities to inform next steps.
Beyond Muscle Contractility
We developed preclinical expertise in the mechanics of skeletal, cardiac and smooth muscle that extends from proteins to tissues to intact animal models. Our translational research in muscle contractility has enabled us to better understand the potential impact of small molecule compounds that increase cardiac or skeletal muscle contractility and to apply those findings to the further evaluation of our drug candidates in clinical populations. In addition to contractility, other major functions of muscle play a role in certain diseases that could benefit from novel mechanism treatments. Accordingly, our knowledge of muscle contractility may serve as an entry point to the discovery of novel treatments for disorders involving muscle functions other than muscle contractility. We are leveraging our current understandings of muscle biology to investigate new ways of modulating these other aspects of muscle function for other potential therapeutic applications.
Manufacturing Resources and Product Supply
Our drug candidates require precise high-quality manufacturing that is compliant with good manufacturing processes (or foreign equivalent) and other applicable laws. We have no manufacturing capabilities and rely on third parties for the supply and sourcing of raw materials, the manufacture of active pharmaceutical ingredients and the manufacture and packaging of finished drug products for both clinical trial materials and commercial supply.
With respect to MYQORZO, we have secured long-term commercial supply agreements with contract manufacturing organizations in Asia, North America and Europe for the supply of raw materials, active pharmaceutical ingredient, finished drug product and both bottle and blister packaging, but each of these arrangements rely on single sources of supply. This strategy increases the risk that our supply chain may be interrupted. To reduce the inherent risk of reliance on single vendors for MYQORZO and mitigate potential interruption of supply, when and where possible, we are embarking on a multi-phase program to adding dual souring CMO's and sites to our global supply chain. We expect this program to take several years to fully execute, receive regulatory approvals and become operational. We have selected suppliers with multiple manufacturing sites and rigorous quality control systems. We are also actively building additional safety stock inventory levels to offset this risk while the longer term dual sourcing strategy is being executed. and have embarked on a project to identify additional suppliers that could be used interchangeably.
For our portfolio of small molecules, we continue to expand our network through third-party contract manufacturers for our CMC and manufacturing needs. These third parties must comply with applicable regulatory requirements, including the FDA's cGMP, the E.U.'s Guidelines on Good Distribution Practice, as well as other stringent regulatory requirements enforced by the FDA or foreign regulatory agencies, as applicable, and are subject to routine inspections. In addition, through our third-party contract manufacturers and data service providers, we continue to provide serialized commercial products as required to comply with the Drug Supply Chain Security Act.
We are mindful of the increasing risks of relying on sole source raw materials from countries where global trade disputes or restrictive legislation are possible. For example, we currently source key registered starting materials for aficamten from manufacturers in China. Although we do not anticipate any immediate difficulties in procuring raw materials from China, we are actively seeking to establish alternative geographically diverse supply arrangements for these particular registered starting materials and other raw materials and compounds.
Competition
There are several companies focused on the development of small molecules for the treatment of HCM, HFrEF, HFpEF and other diseases that MYQORZO and our drug candidates are intended to treat. Our competitors and potential competitors include major pharmaceutical and biotechnology companies, as well as academic research institutions, clinical reference laboratories and government agencies that are pursuing research activities similar to ours. Certain of the organizations competing with us have greater capital resources, larger research and development staff and facilities, deeper regulatory expertise and more extensive product manufacturing and commercial capabilities than we do, which may afford them a competitive advantage.
Competition for MYQORZO
MYQORZO competes with Camzyos® (mavacamten), a cardiac myosin inhibitor marketed by Bristol Myers Squibb, as a therapy for oHCM, along with generic therapies, specifically beta blockers and calcium channel blockers, which are currently considered first-line standard of care. In addition to Camzyos®, Edgewise Therapeutics, Lexicon, Tenaya and Braveheart Bio (Hengrui) are conducting clinical trials and could commercialize a drug that would compete with MYQORZO if successful. Other companies may also be conducting clinical trials and pre-clinical activities in HCM, and if successful, there may be other treatments approved for HCM, some of which may be complementary to MYQORZO and others of which may be competitive.
Camzyos® was approved by the FDA in 2022 with a comprehensive and mandatory REMS. We believe the MYQORZO label and REMS are sufficiently distinct from Camzyos® to be highly competitive in the oHCM market. We believe the oHCM market has the potential to exceed $5 billion in the U.S. and Europe combined by 2035.
We believe that our ability to successfully compete will depend on, among other things:
the efficacy and safety of MYQORZO, both alone and in combination with other therapies;
the timing and scope of regulatory approvals in Europe, Japan and other countries in oHCM and potentially other indications, if at all;
our ability to manufacture quantities of MYQORZO to meet its market demand;
our ability to gain market access and secure coverage and adequate reimbursement in oHCM and potentially other indications, if any;
acceptance of MYQORZO by physicians and other health care providers;
protection of our intellectual property, through enforcement of our intellectual property rights against any challengers, including potential generic competition and the absence of any blocking intellectual property rights that limit our ability to market MYQORZO as we have planned; and
the availability of substantial capital resources to fund development and commercialization activities.
Competition for Omecamtiv Mecarbil
We believe the principal competition for omecamtiv mecarbil, if ultimately approved for sales and marketing by FDA and/or other regulatory agencies for the treatment of HFrEF, includes generic drugs, such as milrinone, dobutamine or digoxin and branded drugs approved for the treatment of HFrEF, such as CORLANOR® (ivabradine) and VERQUVO® (vericiguat). Omecamtiv mecarbil could also compete against other novel drug candidates and therapies in development, such as those being developed by Novartis AG, Merck & Co., Inc., Bayer AG, AstraZeneca PLC, Kardigan, Inc., and Bristol-Myers Squibb Company.
If approved, omecamtiv mecarbil is not intended to compete with guideline directed first line therapies and instead is intended to be a complementary add-on therapy for the subset of heart failure patients with severely reduced ejection fraction. The first line HFrEF generic therapies, including beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs) as well the branded drugs such as ENTRESTO® (sacubitril/valsartan) and the SGLT2 inhibitor class that have either expanded or are planning to expand their labels to include treatment of patients with heart failure, include FORXIGA® (dapagliflozin), INVOKANA® (canagliflozin), and JARDIANCE® (empagliflozin).
The treatment landscape for HFrEF is crowded and evolving, especially given the addition of SGLT2 inhibitors as AHA/ACC/HFSA guideline directed medical therapy for HFrEF. SGLT2 inhibitors have steadily gained market share. In addition, there are a number of medical devices both marketed and in development for the treatment of patients living with heart failure.
We believe that our ability to successfully compete will depend on, among other things:
efficacy and safety of omecamtiv mecarbil, both alone and in combination with other therapies;
the ability to fund and successfully complete an additional confirmatory phase 3 clinical trial of omecamtiv mecarbil in HFrEF and resolve to the satisfaction of FDA the other deficiencies stipulated in the CRL we received in response to our initial NDA submission for omecamtiv mecarbil;
the timing and scope of regulatory approval by EMA and regulatory bodies in other countries, if at all;
our ability to manufacture and sell commercial quantities of omecamtiv mecarbil product to the market;
our ability to gain market access and secure coverage and adequate reimbursement with affordable patient out of pocket cost in approved indications;
product acceptance by physicians and other health care providers;
if required in connection to regulatory approval by FDA, EMA and/or other regulatory authorities, the commercial availability of an antibody-based immunoassay to measure omecamtiv mecarbil concentration levels in patients to whom omecamtiv mecarbil is administered
price competition, particularly of generic products;
protection of our intellectual property through enforcement of our intellectual property rights against any challengers, including potential generic competition, and the absence of any blocking intellectual property rights that limit our ability to market MYQORZO as we have planned; and
the availability of substantial capital resources to fund development and commercialization activities.
Competition for Ulacamten
We believe the principal competition for ulacamten, if ultimately approved for sales and marketing by FDA and/or other regulatory agencies for the treatment of HFpEF will include both in-class cardiac myosin inhibitors as well as general heart failure drugs with HFpEF labels, many of which will be generic. In-class competitive agents that are currently in development include Bristol Myers Squibb's MYK-224, Shandong's HRS-1893 and Edgewise's EDG-15400. Approved drugs with HFpEF labels that will be generic include SGLT2 inhibitors (dapagliflozin and empagliflozin), mineralocorticoid receptor antagonists (finerenone), angiotensin receptor-neprilysin inhibitors (sacubitril/valsartan), and GLP-1 receptor agonists (semaglutide and tirzepatide). We expect that the treatment landscape will continue to evolve as we proceed towards potential regulatory approval. Therefore, ulacamten could also compete against other novel drug candidates and therapies in development, such as those being developed by Eli Lilly, Novo Nordisk, Mission Therapeutics, Cardurion Pharmaceuticals and potentially others that may still move into the clinic before potential approval of ulacamten.
We believe that our ability to successfully compete will depend on, among other things:
the ability to fund and successfully complete pivotal and confirmatory phase 3 clinical trials of ulacamten in HFpEF with demonstrated cardiovascular outcomes and feel/function endpoints;
efficacy, safety and reliability of ulacamten, both alone and in combination with other therapies;
the timing and scope of regulatory approval by FDA, EMA and regulatory bodies in other countries;
our ability to manufacture and sell commercial quantities of ulacamten to the market;
our ability to gain market access and secure coverage and adequate reimbursement with affordable patient out of pocket cost in approved indications; and
product acceptance by physicians and other health care providers.
Intellectual Property Resources
Our policy is to seek patent protection for the technologies, inventions and improvements that we develop and consider important to the advancement of our business. We also rely on trade secrets, technical know-how and continuing innovation to develop and maintain our competitive position.
The following tables list certain granted U.S. and European patents that relate to our commercialization product and our most advanced drug candidate. Additional patent protection through granted patents in the U.S., Europe, or other foreign jurisdictions may be available, and additional patent applications in the U.S., Europe, or other foreign jurisdictions are being pursued. In addition to patent exclusivity, the products and drug candidates may be protected by regulatory exclusivities upon approval in some countries.
Aficamten
The following table describes certain issued U.S. and European patents that relate to aficamten. In addition to the patents listed below, we continue to pursue additional patent applications. At the appropriate time, the Company will pursue available patent term extensions and supplementary protection certificates in the U.S. and Europe that may, if issued, extend exclusivity beyond the patent expirations listed in the table.
Jurisdiction
Patent No.
Patent Type
Patent Expiration*
United States
10,836,755
Composition of matter
2039
United States
12,370,179
Method of treatment
2042
Europe
3740481^
Composition of matter
2039
Europe
3999180^^
Polymorphic forms
2040
Europe
3999038
Formulation
2040
Europe
4370116^^^
Compound for use
2042
*Stated expiration dates do not account for any patent term adjustment, patent term extension, supplementary protection certificates, or pediatric extensions that may be available. For example, on February 4, 2026, the Company filed an application for patent term extension with the U.S. Patent and Trademark Office for U.S. Patent No. 10,836,755, requesting an extension of the term to December 19, 2039, which is 14 years from the date of product approval.
^ In March 2025, Generics [UK] Limited filed an opposition in the European Patent Office (EPO) seeking revocation of European Patent No. 3740481. The Company submitted a response to the opposition in August 2025. An oral hearing is scheduled for June 2026.
^^ In February 2025, Generics [UK] Limited filed an opposition in the European Patent Office (EPO) seeking revocation of European Patent No. 3999180. The Company submitted a response to the opposition in June 2025. An oral hearing is anticipated in this proceeding at a time to be determined by the EPO.
^^^In October 2025, Synthon BV and an anonymous party filed oppositions in the European Patent Office (EPO) seeking revocation of European Patent No. 4370116. The Company is preparing a response. An oral hearing is anticipated in this proceeding at a time to be determined by the EPO.
In Japan, aficamten is protected by issued patents covering the composition of matter, polymorphic forms, and formulations of aficamten that expire between 2039 and 2040. At the appropriate time, the Company will pursue available patent term extension in Japan that may, if issued, extend exclusivity beyond the baseline patent expiration dates. In China, aficamten is protected by issued patents covering the composition of matter, polymorphic forms, and formulations of aficamten that expire between 2039 and 2040. The Company has filed an application for patent term extension for Chinese Patent No. 2019800091285, requesting an extension to December 16, 2039.
Omecamtiv Mecarbil
The following table describes certain issued U.S. and European patents that relate to omecamtiv mecarbil. In addition to the patents listed below, we continue to pursue additional patent applications. At the appropriate time, the Company will pursue available patent term extensions and supplementary protection certificates in the U.S. and Europe that may, if issued, extend exclusivity beyond the patent expirations listed in the table.
Jurisdiction
Patent No.
Patent Type
Patent Expiration*
United States
9,988,354
Salt form
2034
United States
9,951,015
Formulation
2034
United States
11,576,910
Methods of treatment
2038
United States
12,194,039
Method of treatment
2041
Europe
2968173
Formulation
2034
Europe
2970123
Salt form
2034
Europe
3645002
Compound for use
2038
Europe
4243825
Compound for use
2041
*Stated expiration dates do not account for any patent term adjustment, patent term extension, supplementary protection certificates, or pediatric extensions that may be available. If omecamtiv mecarbil is approved, an extension of the U.S. patent term may be available for one patent covering the approved drug, which could extend the term of the applicable patent by up to a maximum of five additional years but not to exceed a total of 14 years from the date of product approval.
In Japan, omecamtiv mecarbil is protected by issued patents covering the salt form and formulation of omecamtiv mecarbil that expire in 2034. In China, omecamtiv mecarbil is protected by issued patents covering the salt form and formulation of omecamtiv mecarbil that expire in 2034. At the appropriate time, the Company will pursue available patent term extensions in Japan and China that may, if issued, extend exclusivity beyond the baseline patent expiration dates.
For a description of the risks relating to our intellectual property, please see the risk factors under Item 1A of this report.
Compliance with Government Regulation
The Regulatory Process for Drug Development
Our business activities, including the manufacturing of our product candidates and our ongoing research and development activities are subject to extensive regulation by numerous governmental authorities in the United States and other countries. Regulation by these government authorities is a significant component in the development, manufacture and commercialization of pharmaceutical products and services. Before marketing in the United States, any new drug developed must undergo rigorous preclinical testing, clinical trials and an extensive regulatory clearance process implemented by the FDA under the Federal Food, Drug, and Cosmetic Act, as amended (the "FDCA"). The FDCA and other various federal, state and foreign statutes govern or influence the research, testing, manufacture, safety, labeling, storage, recordkeeping, approval, promotion, marketing, distribution, post-approval monitoring and reporting, sampling, quality, and import and export of our medicines. State, local, and other authorities also regulate pharmaceutical manufacturing.
Applicable legislation requires licensing of manufacturing and contract research facilities, carefully controlled research and testing of products, and governmental review and/or approval of results prior to marketing therapeutic products. Additionally, adherence to GLPs and cGCPs during nonclinical and clinical testing and cGMP during production is required. Our manufacturing CMOs are subject to periodic inspection by the FDA and other foreign equivalents to ensure that they are operating in compliance with cGMP requirements. In addition, marketing authorization for each new medicine may require a rigorous manufacturing pre-approval inspection by regulatory authorities. Post approval, there are strict regulations regarding changes to the manufacturing process, and, depending on the significance of the change, changes may require prior FDA approval. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting and documentation requirements upon us and any third-party manufacturers that we may decide to use.
In addition, we are subject to other state and federal laws, including, among others, anti-kickback laws, fraud and abuse, false claims laws, Sunshine Act, patient protection and affordable care, data privacy and security laws and regulations, and transparency laws that restrict certain business practices in the pharmaceutical industry. Violations of these healthcare laws can result in significant penalties, including civil, criminal and administrative penalties. Moreover, government coverage and reimbursement policies will both directly and indirectly impact our ability to successfully commercialize any future approved products, and such coverage and reimbursement policies will be impacted by enacted and any applicable future healthcare reform and drug pricing measures. Further, the United States and some foreign jurisdictions may consider and enact additional legislative and regulatory initiatives to change the healthcare system and modify these laws in ways that could affect the pharmaceutical industry.
U.S. Pharmaceutical Product Development Process
Prior to beginning any clinical trial with a product candidate in the United States, we must submit an IND to the FDA. An IND is a request for authorization from the FDA to administer an investigational new drug product to humans and must become effective before human clinical trials may begin. Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with GCPs, which include the requirement that all research subjects provide their informed consent for their participation in any clinical study. Clinical trials are conducted under protocols detailing, among other things, the objectives of the study, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. Furthermore, an independent institutional review board ("IRB") for each site proposing to conduct the clinical trial must review and approve the plan for any clinical trial and its informed consent form before the clinical trial begins at that site and must monitor the study until completed. Regulatory authorities, the IRB or the company may suspend a clinical trial at any time on various grounds, including a finding that the subjects are being exposed to an unacceptable health risk or that the trial is unlikely to meet its stated objectives. For purposes of NDA approval, human clinical trials are typically conducted in three sequential phases that may overlap.
Phase 1. The investigational product is initially introduced into healthy human subjects or patients with the target disease or condition. These studies are designed to test the safety, dosage tolerance, absorption, metabolism and distribution of the investigational product in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness.
Phase 2. The investigational product is administered to a limited patient population with a specified disease or condition to evaluate the preliminary efficacy, optimal dosages and dosing schedule and to identify possible adverse side effects and safety risks. Multiple Phase 2 clinical trials may be conducted to obtain information prior to beginning larger and more expensive Phase 3 clinical trials.
Phase 3. The investigational product is administered to an expanded patient population to further evaluate dosage, to provide statistically significant evidence of clinical efficacy and to further test for safety, generally at multiple geographically dispersed clinical trial sites. These clinical trials are intended to establish the overall risk/benefit ratio of the investigational product and to provide an adequate basis for product approval.
In some cases, the FDA may require, or companies may voluntarily pursue, additional clinical trials after a product is approved to gain more information about the product. These so-called Phase 4 studies may be made a condition to approval of the NDA.
Companies may choose, but are not required, to conduct a foreign clinical study under an IND. When a foreign clinical study is conducted under an IND, all IND requirements must be met unless waived. When the foreign clinical study is not conducted under an IND, the company must ensure that the study complies with certain FDA regulatory requirements in order to use the study as support for an IND or application for marketing approval or licensure, including that the study was conducted in accordance with GCP, including review and approval by an independent ethics committee and use of proper procedures for obtaining informed consent from subjects, and the FDA is able to validate the data from the study through an onsite inspection if the FDA deems such inspection necessary. The GCP requirements encompass both ethical and data integrity standards for clinical studies.
To establish a new product candidate's safety and efficacy, the FDA requires companies seeking approval to market a pharmaceutical drug product to submit extensive preclinical and clinical data, along with other information, for each indication for which the product will be labeled. The data and information are submitted to the FDA in the form of a New Drug Application, or NDA, which must be accompanied by payment of a significant user fee unless a waiver or exemption applies. Generating the required data and information for an NDA takes many years and requires the expenditure of substantial resources. Information generated in this process is susceptible to varying interpretations that could delay, limit or prevent regulatory approval at any stage of the process. The failure to demonstrate adequately the quality, safety and efficacy of a product candidate under development would delay or prevent regulatory approval of the product candidate. Under applicable laws and FDA regulations, each NDA submitted for FDA approval is given an internal administrative review within 60 days following submission of the NDA. If deemed sufficiently complete to permit a substantive review, the FDA will "file" the NDA. The FDA can refuse to file any NDA that it deems incomplete or not properly reviewable. The FDA has established internal goals of eight months from submission for priority review of NDAs that cover new product candidates that offer major advances in treatment or provide a treatment where no adequate therapy exists, and 12 months from submission for the standard review of NDAs. However, the FDA is not legally required to complete its review within these periods, these performance goals may change over time and the review is often extended by FDA requests for additional information or clarification. Moreover, the outcome of the review, even if generally favorable, may not be an actual approval but a "complete response letter" that describes additional work that must be done before the NDA can be approved. Before approving an NDA, the FDA can choose to inspect the facilities at which the product is manufactured and will not approve the product unless the manufacturing facility complies with cGMPs. The FDA may also audit sites at which clinical trials have been conducted to determine compliance with cGCPs and data integrity. The FDA's review of an NDA may also involve review and recommendations by an independent FDA advisory committee, particularly for novel indications. The FDA is not bound by the recommendation of an advisory committee. Further, the FDA may require that certain contraindications, warnings or precautions be included in the product labeling.
In addition, under the Pediatric Research Equity Act (PREA), an NDA or supplement to an NDA must contain data to assess the safety and effectiveness of the drug product candidate for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The Food and Drug Administration Safety and Innovation Act requires that a company who is planning to submit a marketing application for a drug product that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial pediatric study plan (PSP). Unless otherwise required by regulation, PREA does not apply to any drug product for an indication for which orphan designation has been granted, except that the PREA will apply to an original NDA for a new active ingredient that is orphan-designated if the drug is a molecularly targeted cancer product intended for the treatment of an adult cancer and is directed at a molecular target that the FDA determines to be substantially relevant to the growth or progression of a pediatric cancer.
If regulatory approval of a product is granted, such approval will be granted for particular indications and may entail limitations on the indicated uses for which such product may be marketed. For example, the FDA may approve the NDA with a REMS to ensure the benefits of the product outweigh its risks. A REMS is a safety strategy to manage a known or potential serious risk associated with a product and to enable patients to have continued access to such medicines by managing their safe use, and could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. The FDA also may condition approval on, among other things, changes to proposed labeling or the development of adequate controls and specifications. Once approved, the FDA may withdraw the product approval if compliance with pre-and post-marketing requirements is not maintained or if problems occur after the product reaches the marketplace. The FDA may require one or more Phase 4 post-market studies and surveillance to further assess and monitor the product's safety and effectiveness after commercialization, and may limit further marketing of the product based on the results of these post-marketing studies.
Orphan Drug Designation and Exclusivity
Under the Orphan Drug Act of 1983, the FDA may grant orphan drug designation to a product candidate intended to treat a rare disease or condition, Orphan drug designation must be requested before submitting an NDA. After the FDA grants orphan drug designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA. The orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review or approval process.
If a product that has orphan drug designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan drug exclusive approval (or exclusivity), which means that the FDA may not approve any other applications, including a full NDA, to market the same product for the same indication for seven years, except in limited circumstances. Orphan drug exclusivity does not prevent the FDA from approving a different drug for the same disease or condition, or the same drug for a different disease or condition.
A designated orphan drug may not receive orphan drug exclusivity if it is approved for a use that is broader than the indication for which it received orphan drug designation. In addition, exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.
There is some uncertainty with respect to the FDA's interpretation of the scope of orphan drug exclusivity. Historically, exclusivity was specific to the orphan indication for which the drug was approved. As a result, the scope of exclusivity was interpreted as preventing approval of a competing product. However, in 2021, the federal court in Catalyst Pharmaceuticals, Inc. v. Becerra suggested that orphan drug exclusivity covers the full scope of the orphan-designated "disease or condition" regardless of whether a drug obtained approval for a narrower use.
Post Approval Requirements
Any products manufactured or distributed by us pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to record-keeping, reporting of adverse experiences, periodic reporting, product sampling and distribution, and advertising and promotion of the product. After approval, most changes to the approved product, such as adding new indications or other labeling claims, are subject to prior FDA review and approval. There also are continuing user fee requirements, under which the FDA assesses an annual program fee for each product identified in an approved NDA. Drug manufacturers and their subcontractors are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMPs, which impose certain procedural and documentation requirements upon us and our third-party manufacturers. Changes to the manufacturing process are strictly regulated, and, depending on the significance of the change, may require prior FDA approval before being implemented.
FDA regulations also require investigation and correction of any deviations from cGMPs and impose reporting requirements upon us and any third-party manufacturers that we may decide to use. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMPs and other aspects of regulatory compliance.
The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical studies to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program. Other potential consequences include, among other things
restrictions on the marketing or manufacturing of a product, complete withdrawal of the product from the market or product recalls;
fines, warning letters or holds on post-approval clinical studies;
refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of existing product approvals;
product seizure or detention, or refusal of the FDA to permit the import or export of products;
consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs;
mandated modification of promotional materials and labeling and the issuance of corrective information;
the issuance of safety alerts, Dear Healthcare Provider letters, press releases and other communications containing warnings or other safety information about the product; or
injunctions or the imposition of civil or criminal penalties.
The FDA closely regulates the marketing, labeling, advertising and promotion of drugs. A company can make only those claims relating to safety and efficacy that are approved by the FDA and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses. Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties.
Abbreviated New Drug Applications for Generic Drugs
In 1984, with passage of the Drug Price Competition and Patent Term Restoration Act of 1984 (commonly referred to as the "Hatch-Waxman Amendments") amending the Federal Food, Drug, and Cosmetic Act ("FDCA"), Congress authorized the FDA to approve generic drugs that are the same as drugs previously approved by the FDA under the NDA provisions of the statute. To obtain approval of a generic drug, an applicant must submit an abbreviated new drug application ("ANDA") to the agency. Upon approval of an ANDA, the FDA indicates that the generic product is "therapeutically equivalent" to the drug product previously approved under an NDA, known as the reference listed drug ("RLD"), and it assigns a therapeutic equivalence rating to the approved generic drug in its publication "Approved Drug Products with Therapeutic Equivalence Evaluations," also referred to as the "Orange Book. Physicians and pharmacists consider the therapeutic equivalence rating to mean that a generic drug is fully substitutable for the RLD.
Under the Hatch-Waxman Amendments, the FDA may not approve an ANDA until any applicable period of nonpatent exclusivity for the RLD has expired. The FDCA provides a period of five years of data exclusivity for NDAs containing a new chemical entity. In cases where such exclusivity has been granted, an ANDA may not be filed with the FDA until the expiration of five years unless the submission is accompanied by a Paragraph IV certification (discussed further below), in which case the applicant may submit its application four years following the original product approval. The FDCA also provides for a period of three years of exclusivity if the NDA includes reports of one or more new clinical investigations, other than bioavailability or bioequivalence studies, that were conducted by or for the applicant and are essential to the approval of the application.
Hatch-Waxman Patent Certification and the 30 Month Stay
Upon approval of an NDA or a supplement thereto, NDA sponsors are required to list with the FDA each patent with claims that cover the applicant's product or a method of using the product. When an ANDA applicant files its application with the FDA, the applicant is required to certify to the FDA concerning any patents listed for the reference product in the Orange Book, except for patents covering methods of use for which the ANDA applicant is not seeking approval.
A certification that the new product will not infringe the already approved product's listed patents or that such patents are invalid or unenforceable is called a Paragraph IV certification. If the applicant does not challenge the listed patents or indicate that it is not seeking approval of a patented method of use, the ANDA application will not be approved until all the listed patents claiming the referenced product have expired. The filing of a patent infringement lawsuit automatically prevents the FDA from approving the ANDA until the earlier of 30 months, expiration of the patent, settlement of the lawsuit or a decision in the infringement case that is favorable to the ANDA applicant.
505(b)(2) New Drug Applications
As an alternative path to FDA approval for modifications to formulations or uses of products previously approved by the FDA pursuant to an NDA, an applicant may submit an NDA under Section 505(b)(2) of the FDCA. Section 505(b)(2) was enacted as part of the Hatch-Waxman Amendments and permits the filing of an NDA where at least some of the information required for approval comes from studies not conducted by, or for, the applicant, and for which the applicant has not obtained a right of reference. If the 505(b)(2) applicant can establish that reliance on the FDA's previous findings of safety and effectiveness is scientifically and legally appropriate, it may eliminate the need to conduct certain preclinical studies or clinical trials of the new product.
To the extent that a Section 505(b)(2) applicant is relying on studies conducted for an already approved product, the applicant is required to certify to the FDA concerning any patents listed for the approved product in the Orange Book to the same extent that an ANDA applicant would. As a result, approval of a 505(b)(2) NDA can be stalled until all the listed patents claiming the referenced product have expired, until any non-patent exclusivity, such as exclusivity for obtaining approval of a new chemical entity, listed in the Orange Book for the referenced product has expired, and, in the case of a Paragraph IV certification and subsequent patent infringement suit, until the earlier of 30 months, settlement of the lawsuit or a decision in the infringement case that is favorable to the Section 505(b)(2) applicant.
Patent Term Extension
In the U.S., after an NDA is approved, owners of relevant drug patents may apply for up to a five-year patent extension, which permits patent term restoration as compensation for the patent term lost during the FDA regulatory process. The allowable patent term extension is typically calculated as one-half the time between, the latter of the effective date of an IND and issue date of the patent for which extension is sought, and the submission date of an NDA, plus the time between NDA submission date and the NDA approval date up to a maximum of five years. The time can be shortened if the FDA determines that the applicant did not pursue approval with due diligence. The total patent term after the extension may not exceed 14 years from the date of product approval. Only one patent applicable to an approved drug product is eligible for extension and only those claims covering the product, a method for using it, or a method for manufacturing it may be extended and the application for the extension must be submitted prior to the expiration of the patent in question. However, we may not be granted an extension because of, for example, failing to exercise due diligence during the testing phase or regulatory review process, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements. Some, but not all, foreign jurisdictions possess patent term extension or other additional patent exclusivity mechanisms that may be more or less stringent and comprehensive than those of the U.S.
Pharmaceutical Coverage, Pricing and Reimbursement
In the United States and markets in other countries, sales of any products for which we receive regulatory approval for commercial sale will depend in part on the availability of coverage and adequate reimbursement from third-party payors, including government authorities, managed care providers, private health insurers and other organizations. In the United States, private health insurers and other third-party payors often provide reimbursement for products and services based on the level at which the government (through the Medicare or Medicaid programs) provides reimbursement for such products and services. There is no uniform coverage and reimbursement policy among third-party payors in the United States; however, private third-party payors often follow Medicare coverage policy and payment limitations in setting their own reimbursement rates. Third-party payors are increasingly examining the medical necessity and cost-effectiveness of medical products and services in addition to their safety and efficacy and, accordingly, significant uncertainty exists as to the coverage and reimbursement status of newly approved therapeutics.
In particular, in the United States, the European Union and other potentially significant markets for our product candidates, government authorities and third-party payors are increasingly attempting to limit or regulate the price of medical products and services, particularly for new and innovative products and therapies, which often has resulted in average selling prices that are lower than they would otherwise be. Third-party payors are increasingly challenging the prices charged for medical products and services, examining the medical necessity and reviewing the cost effectiveness of pharmaceutical products, medical devices and medical services, in addition to questioning safety and efficacy. Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit sales of any product that receives approval.
Moreover, the U.S. government and state legislatures have continued implementing cost-containment programs, including price controls and restrictions on coverage and reimbursement and requirements for substitution of generic products. The IRA provides CMS with significant new authorities intended to curb drug costs and to encourage market competition. For the first time, CMS will be able to directly negotiate prescription drug prices and to cap out-of-pocket costs. Each year, CMS will select and negotiate a preset number of high-spend drugs that are covered under Medicare Part B and Part D that do not have generic or biosimilar competition. Since 2023, 25 Medicare Part D drugs have become subject to price negotiations. The IRA also provides a new "inflation rebate" covering Medicare patients that took effect in 2023 and is intended to counter certain price increases in prescriptions drugs. The inflation rebate provision requires drug manufacturers to pay a rebate to the federal government if the price for a drug under Medicare Part B and Part D increases faster than the rate of inflation. Notwithstanding these provisions, the IRA's impact on commercialization and competition remains largely uncertain.
In addition, net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the U.S. Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for medical products. We cannot be sure that reimbursement will be available for any product candidate that we may commercialize and, if reimbursement is available, the level of reimbursement.
Moreover, there has recently been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed and enacted federal and state measures designed to, among other things, reduce the cost of prescription drugs, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug products. For example, in May 2025, the Trump Administration renewed the idea of international reference pricing through an executive order entitled "Delivering Most-Favored-Nation Prescription Drug Pricing to American Patients", which, among other things, directs the U.S. Department of Health and Human Services ("HHS") and other agencies to communicate most-favored-nation price targets to pharmaceutical manufacturers to bring prices for U.S. patients in line with comparably developed nations and to facilitate direct-to-consumer purchasing programs. HHS subsequently issued guidance indicating the MFN target price will be the lowest price paid in an Organization for Economic Co-operation and Development country with a gross domestic product, or GDP, per capita of at least 60% of the U.S. GDP per capital. In addition, in late 2025, CMS proposed new drug payment models to lower drug prices for Medicare and Medicaid beneficiaries; under the models, CMS would explore potential adjustments to drug rebate calculations by comparison to international drug pricing information.
Individual states in the U.S. have also become increasingly active in passing legislation and implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain drug access and marketing cost disclosure and transparency measures, and encourage importation from other countries and bulk purchasing.
These developments will put additional pressure on product pricing, reimbursement and utilization, which may adversely affect our future product sales and results of operations. These pressures can arise from rules and practices of managed care groups, judicial decisions and governmental laws and regulations related to Medicare, Medicaid and healthcare reform, pharmaceutical reimbursement policies and pricing in general. As a result, coverage and adequate third-party reimbursement may not be available for our product candidates to enable us to realize an appropriate return on our investment in research and product development.
The market for MYQORZO and any of our other products for which we receive regulatory approval for commercial sale depends significantly on access to third-party payors' drug formularies or lists of medications for which third-party payors provide coverage and reimbursement. The industry competition to be included in such formularies often leads to downward pricing pressures on pharmaceutical companies. Also, third-party payors may refuse to include a particular branded drug in their formularies or may otherwise restrict patient access to a branded drug when a less costly generic equivalent or other alternative is available. In addition, because each third-party payor individually approves coverage and reimbursement levels, obtaining coverage and adequate reimbursement is a time-consuming and costly process. We would be required to provide scientific and clinical support for the use of any product to each third-party payor separately with no assurance that approval would be obtained, and we may need to conduct expensive pharmacoeconomic studies in order to demonstrate the cost-effectiveness of our products. This process could delay the market acceptance of any of our product candidates for which we may receive approval and could have a negative effect on our future revenue and operating results. We cannot be certain that our product candidates will be considered cost-effective. If we are unable to obtain coverage and adequate payment levels for our product candidates from third-party payors, physicians may limit how much or under what circumstances they will prescribe or administer them, and patients may decline to purchase them. This in turn could affect our ability to successfully commercialize our products and impact our profitability, results of operations, financial condition, and future success.
Cytokinetics Human Capital
As of December 31, 2025, we had 673 employees.
We are committed to fostering and maintaining a culture that engenders collaboration and teamwork, inclusion, respect, transparency and candor. We provide our employees with an array of professional development resources and tools to support their learning, growth and development opportunities. We prioritize safety and endeavor to eliminate workplace incidents, risks and hazards through the implementation of our safety policies and standards. We have adopted a flexible, hybrid working arrangement for our employees, allowing some of our employees to work remotely during certain days of the week. We were honored to be recognized as a San Francisco Times Great Place to Work in 2025.
Our compensation and benefit programs are designed to enable us to attract and retain the best employees in a very competitive life science sector and we regularly benchmark and survey the market so that we maintain competitive programs. In addition, we routinely survey our employees to measure engagement, identify and take action on opportunities for improvement, and share these results with employees.
We have a rigorous annual goal setting and goal evaluation process under the supervision of the Compensation and Talent Committee of our Board of Directors and senior management to assist our employees in understanding what is expected of them individually and as an organization.
Our Compensation and Talent Committee of the Board of Directors regularly reviews employee engagement, reward programs, human resource metrics, including attrition, retention and staffing.
Investor Information
We file electronically with the SEC our annual reports on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K pursuant to Section 13 or 15(d) of the Exchange Act. The SEC maintains an Internet site at https://www.sec.gov that contains reports, proxy and information statements, and other information regarding issuers that file electronically with the SEC.
ITEM 1A. RISK FACTORS
In evaluating our business, you should carefully consider the following risks in addition to the other information in this report. Any of the following risks could materially and adversely affect our business, results of operations, financial condition, cash flows, reputation or your investment in our securities, and many are beyond our control. The risks and uncertainties described below are not the only ones facing us. Additional risks and uncertainties not presently known to us, or that we currently see as immaterial, may also adversely affect our business. The disclosures in this section reflect our beliefs and opinions as to factors that could materially and adversely affect us in the future. References to past events are provided by way of example only and are not intended to be a complete listing or a representation as to whether or not such factors have occurred in the past. The information discussed below should be considered carefully with the other information contained in this Annual Report on Form 10-K and the other documents and materials we file with the SEC, as well as news releases and other information we publicly disseminate from time to time.
Risks Specific to our Company in connection with our Commercial Operations
If physicians and patients do not accept our drugs, we may be unable to generate significant revenue, if any.
MYQORZO may not gain market acceptance among physicians, healthcare payors, patients and the medical community, and our other drug candidates, if approved, may similarly fail to gain market acceptance. Even if the clinical safety and efficacy of drugs developed from our drug candidates are established for purposes of approval, physicians may elect not to recommend these drugs for a variety of reasons including, but not limited to the availability of competitive drugs to the market, cost-effectiveness, availability of insurance coverage and reimbursement, convenience and ease of administration, prevalence and severity of adverse events, HCP practice patterns and familiarity with earlier to market therapies.
The size of the potential market for MYQORZO or our product candidates is difficult to estimate and, if any of our assumptions are inaccurate, the actual markets for our products or product candidates may be smaller than our estimates. If the market opportunities for any products or product candidates we develop are smaller than we believe they are, or if any approval that we obtain is based on a narrower definition of the patient population, our potential revenues may be adversely affected, and our business may suffer.
Our potential market opportunity for oHCM, nHCM, and other indications is based on internal and third-party estimates and resources, including, without limitation, our estimates and research, as well as industry and general publications and research, surveys and studies conducted by Cytokinetics and third parties, which may be incorrect. Our estimated potential market opportunity for cardiac myosin inhibitors in oHCM and nHCM is based on the following assumptions: our understanding of the prevalence of HCM in the general population from published epidemiological studies and analysis of longitudinal claims data, the percentage split of diagnosed oHCM and nHCM patients derived from publications, market research and patient transaction databases, the percentage of available symptomatic patients not adequately managed by the current standard of care among diagnosed HCM patients, rates of patient compliance and persistence, based on patient transaction database and/or third-party market research. The conditions supporting our assumptions or estimates and the market data supporting these assumptions and estimates may change at any time or otherwise be inaccurate, thereby reducing the predictive accuracy of these underlying factors.
Our total addressable market will ultimately depend upon, among other things, the willingness of patients and HCPs to utilize MYQORZO compared to other cardiac sarcomere inhibitors or other therapies, the number of actual treatable symptomatic patients on MYQORZO and other cardiac myosin inhibitors or other therapies over time, the subset of eligible HCM patients who may utilize MYQORZO, acceptance and accessibility of our drug products by the medical community and patients, market share, drug pricing and reimbursement across payer types (i.e., Medicare, commercial, Medicaid, etc.). The number of patients within the United States and other major markets and elsewhere may turn out to be materially lower than expected, patients may not be otherwise amenable to treatment with our drugs or new patients may become increasingly difficult to identify or gain access to, all of which would harm our results of operations and our business. If our conclusions, analysis or internally generated data prove to be inaccurate or we make errors in our assumptions based on that data, our total addressable market may be meaningfully smaller than we have estimated, our future growth opportunities and sales growth may be impaired, any of which could have a material adverse effect on our business, financial condition and results of operations.
Our competitors may develop drugs that are less expensive, safer and/or have similar or better efficacy than ours, which may diminish or eliminate the commercial success of any drugs that we may commercialize.
We compete with companies that have developed drugs or are developing drug candidates for cardiovascular diseases, diseases and conditions associated with muscle weakness or wasting and other diseases for which our drug candidates may be useful treatments. We also compete for market share against large pharmaceutical and biotechnology companies and smaller companies that are collaborating with larger pharmaceutical companies, new companies, academic institutions, government agencies and other public and private research organizations. Many of these competitors, either alone or together with their partners, develop new drug candidates that can compete with ours. Many of these competitors have larger research and development programs or substantially greater financial resources than we do. If our competitors market drugs that are less expensive, safer and/or have similar or better efficacy than MYQORZO, or any other drugs that we may commercialize in the future, or that reach the market sooner than MYQORZO, or any other drugs that we may commercialize in the future, we may not achieve commercial success.
The commercial success of our products depends on the availability and sufficiency of third-party payor and/or government for coverage and reimbursement.
Patients in the United States and elsewhere generally rely on third-party payors and/or governments to reimburse part or all of the costs associated with their prescription drugs. Accordingly, market acceptance of our products is dependent on the extent to which third-party coverage and reimbursement is available from government health administration authorities (including in connection with government healthcare programs, such as Medicare and Medicaid in the United States), private healthcare insurers and other healthcare funding organizations. Significant uncertainty exists as to the coverage and reimbursement status of any products for which we may obtain regulatory approval. Even if we obtain coverage for a given drug product, the timeframe from approval to coverage could be lengthy, inadequate, and/or the associated reimbursement rate may not be adequate to cover our costs, including research, development, intellectual property, manufacture, sale and distribution expenses, or may require co-payments that patients find unacceptably high.
We historically have had limited interactions and relationships with payors. Our ability to engage with US payors and secure coverage may improve as we commercialize MYQORZO and generate additional clinical and real-world evidence. Over time, we anticipate our drugs will be adopted by our patients as indicated by their labels. To achieve this adoption, our drugs will need to be widely reimbursed via medical exception or listed in formularies of major pharmacy benefit managers and payors in the U.S. These major pharmacy benefit managers and payors include Medicare, Medicaid, VA, DoD, TriCare, and commercial payors. The process to achieve coverage with pharmacy benefit managers and payors can be time consuming, is not guaranteed and if achieved can impact profitability given the level of rebates often required.
Coverage and reimbursement policies for drug products can differ significantly from payor to payor as there is no uniform policy of coverage and reimbursement for drug products among third-party payors in the United States. There may be significant delays in obtaining coverage and reimbursement as the process of determining coverage and reimbursement is often time-consuming and costly which will require us to provide scientific and clinical support for the use of our products to each payor separately, with no assurance that coverage or adequate reimbursement will be obtained. It is difficult to predict at this time what third parties will decide with respect to coverage and reimbursement for our products. Coverage policies and third-party reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.
In addition, there is significant uncertainty regarding the reimbursement status of newly approved healthcare products. We may need to conduct expensive pharmacoeconomic studies to demonstrate the cost-effectiveness of our products. If third-party payors do not consider our products to be cost-effective compared to other therapies, the payors may not cover our products as a benefit under their plans, or if they do, the level of payment may not be sufficient to allow us to sell our products on a profitable basis.
Additionally, to the extent required by regulatory authorities for the safe and effective use of any of our drug products, we or our partners may develop companion diagnostic tests for use with our products or product candidates such as with omecamtiv mecarbil. Companion diagnostic tests require coverage and reimbursement separate and apart from the coverage and reimbursement for their companion pharmaceutical or biological products. Similar challenges to obtaining coverage and reimbursement, applicable to pharmaceutical products, will apply to companion diagnostics and could adversely impact the commercial prospects of omecamtiv mecarbil or any other drug we may develop that requires a companion diagnostic test.
If we are unable to obtain and maintain sufficient third-party coverage and adequate reimbursement for our products, the commercial success of MYQORZO, as well as any future marketed drug products may be greatly hindered and our financial condition and results of operations may be materially and adversely affected.
We have no manufacturing capabilities and depend on single source contract manufacturers to produce our commercial product and clinical trial materials, including our drug candidates, and will have continued reliance on contract manufacturers for the development and commercialization of our potential drugs.
We do not operate manufacturing facilities for clinical or commercial production of our drugs and drug candidates. We lack the resources and the capabilities to manufacture any of our drug candidates on a clinical or commercial scale.
In addition, under our license and collaboration agreements, we have committed to providing Sanofi and Bayer with supply of aficamten for development and commercialization of MYQORZO in China, Taiwan and Japan, which we will have to source from our contract manufacturers.
We currently rely on single source CMOs for the manufacture of any or all of MYQORZO as a finished drug product and the active pharmaceutical ingredient and registered starting materials used in the production of MYQORZO. We also rely on a single source CMO for the packaging of MYQORZO in blister packaging for use in Europe. If these CMOs fail to provide us with sufficient quantities of product or fail to comply with manufacturing regulations, our business could be harmed. Switching CMOs or manufacturing sites would be difficult and time-consuming because the number of potential CMOs is limited. In addition, before a drug from any replacement CMO or manufacturing site can be commercialized, the FDA and, in some cases, foreign regulatory agencies, must approve that site. These approvals would require regulatory testing and compliance inspections. A new CMO or manufacturing site also would have to be educated in, or develop substantially equivalent processes for, production of our drugs and drug candidates. It may be difficult or impossible to transfer certain elements of a manufacturing process to a new CMO or for us to find a replacement CMO on acceptable terms quickly, or at all, either of which would delay or prevent our ability to develop drug candidates and commercialize any resulting drugs.
We also expect to rely on single source CMOs to supply all future drugs and drug candidates for which we conduct development, as well as other materials required to conduct our clinical trials, and to fulfil our obligations under our license and collaboration agreements. If our existing or future CMOs fail to, or are unable to perform satisfactorily or if any of the raw materials, drug substance, or drug products are subject to restrictive import/export controls or tariffs, it could impede commercialization or delay development or regulatory approval of our drug candidates or commercialization of our drugs, producing additional losses and depriving us of potential product revenues, and also lead to our breach of one of our license and collaboration agreements, giving rise to the ability to terminate such agreements and other adverse consequences as stipulated in such agreements. In addition, if a CMO fails to, or is unable to, perform as agreed, our ability to collect damages may be contractually limited.
Finally, the United States and other countries have imposed and may continue to impose new trade restrictions and export regulations, have levied tariffs and taxes on certain goods, including the potential for tariffs applicable to pharmaceutical products and their inputs. In September 2025, the United States administration announced plans to impose up to 100% tariffs on imported branded or patented pharmaceutical products, subject to certain exceptions. There is substantial uncertainty as to when such tariffs may go into effect and whether such tariffs would apply to the importation of registered starting materials, active pharmaceutical ingredients or bulk drug products that we use in our business, and, more generally, about the duration of existing tariffs, implementation of announced tariffs, litigation challenging tariffs and whether additional tariffs or other retaliatory measures may be imposed, modified or suspended. If additional tariffs, trade restrictions or other barriers are imposed or expanded, our costs for raw materials, active pharmaceutical ingredients, finished drug product or other inputs could increase materially, and our supply chain could be disrupted, which could materially adversely affect our business, financial condition and results of operations.
We may not be able to successfully manufacture our drugs or drug candidates in sufficient quality and quantity, which would delay or prevent us from developing our drug candidates and commercializing approved drug products.
Prior to the recent approval of MYQORZO in December 2025, our drug candidates had been manufactured in quantities adequate only for preclinical studies and early through late-stage clinical trials. In order to conduct large scale clinical trials for a drug candidate and for commercialization of the resulting drug if that drug candidate is approved for sale, such as for MYQORZO, we need to manufacture drugs in larger quantities and validate the repeatability of those manufacturing processes. We may not be able to successfully repeat or increase the manufacturing capacity for any of our drugs or drug candidates, in a timely or cost-effective manner or at all. Significant changes or scale-up of manufacturing may require additional validation studies, which are costly and which regulatory authorities must review and approve. In addition, quality issues may arise during those changes or scale-up activities because of the inherent properties of a drug or drug candidate itself or of a drug or drug candidate in combination with other components added during the manufacturing and packaging process, or during shipping and storage of the finished product or active pharmaceutical ingredients.
Our drug candidates and commercialized drugs, such as MYQORZO, require precise high-quality manufacturing. The failure to achieve and maintain high manufacturing standards in compliance with cGMP, including failure to document and detect, control, analyze and resolve anticipated or unanticipated manufacturing errors or the frequent occurrence of such errors, could result in patient injury or death, discontinuance or delay of ongoing or planned clinical trials, delays or failures in product testing or delivery or regulatory approval, cost overruns, product recalls or withdrawals and other problems that could seriously hurt our business. Contract drug manufacturers often encounter difficulties involving production yields, quality control and quality assurance and shortages of qualified personnel. These manufacturers are subject to stringent regulatory requirements, including cGMPs, regulations and similar foreign laws and standards. Each contract manufacturer must pass a pre-approval inspection before we can obtain marketing approval for any of our drug candidates and following approval will be subject to ongoing periodic unannounced inspections by the FDA, the
U.S. Drug Enforcement Agency and other regulatory agencies, to ensure strict compliance with cGMPs and other applicable government regulations and corresponding foreign laws and standards. We seek, and require our contract manufacturers, to comply fully with all applicable regulations, laws and standards. However, we do not have control over our contract manufacturers' compliance with these regulations, laws and standards. If one of our contract manufacturers fails to pass its pre-approval inspection or maintain ongoing compliance at any time, the production of our drugs or drug candidates could be interrupted, negatively impacting commercialization efforts for our approved drug products or resulting in delays or discontinuance of our clinical trials or refusal of regulatory approval for our drug candidates, leading to additional costs and potentially lost revenues. In addition, failure of any third-party manufacturers or us to comply with applicable regulations, including pre- or post-approval inspections and the cGMP requirements of the FDA or other comparable regulatory agencies, could result in sanctions being imposed on us. These sanctions could include fines, injunctions, civil penalties, failure of regulatory authorities to grant marketing approval of our products, delay, suspension or withdrawal of approvals, license revocation, product seizures or recalls, operational restrictions and criminal prosecutions, any of which could significantly and adversely affect our business.
Disclaimer
Cytokinetics Incorporated published this content on April 17, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on April 17, 2026 at 23:23 UTC.